This phase I trial is studying the side effects and best dose of GTI-2040 and high-dose cytarabine in treating patients with refractory or relapsed acute myeloid leukemia. GTI-2040 may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth. Drugs used in chemotherapy, such as cytarabine, use different ways to stop cancer cells from dividing so they stop growing or die. Giving GTI-2040 together with cytarabine may kill more cancer cells.

Maximum-tolerated dose (MTD) as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 [ Time Frame: Up to day 42 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Therapeutic response [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]

Standard paired statistical tests, parametric and nonparametric, will be used to baseline with treatment values. With data collected serially over time, repeated measures analysis of variance will be used to analyze data.

Change in R2 expression in circulating and marrow leukemia cells [ Time Frame: From baseline to up to 6 years ] [ Designated as safety issue: No ]

Standard paired statistical tests, parametric and nonparametric, will be used to baseline with treatment values. With data collected serially over time, repeated measures analysis of variance will be used to analyze data.

I. Determine the therapeutic response in patients treated with this regimen. II. Determine the pharmacokinetics of this regimen in these patients.

OUTLINE: This is a dose-escalation study. Patients are stratified according to age (under age 60 vs age 60 and over). Patients are assigned to 1 of 2 strata.

Stratum I (under age 60): Patients receive GTI-2040 IV continuously on days 1-6 and high-dose cytarabine IV over 2 hours twice daily on days 2, 4, and 6.

Stratum II (age 60 and over): Patients receive GTI-2040 IV continuously on days 1-6 and high-dose cytarabine IV over 4 hours once daily on days 2-6.

In both strata, treatment continues in the absence of unacceptable toxicity.

Cohorts of 3-6 patients per stratum receive escalating doses of GTI-2040 and high-dose cytarabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

PROJECTED ACCRUAL: A total of 6-51patients will be accrued for this study within 2-16 months.

Eligibility

Ages Eligible for Study:

18 Years and older

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Histologically confirmed acute myeloid leukemia according to the WHO classification

Relapsed or refractory disease, meeting 1 of the following criteria:

Unresponsive to initial treatment

Recurrent disease after treatment with prior conventional or high-dose chemotherapy with or without stem cell support

CNS involvement allowed provided there are no residual leukemic cells detected in the cerebrospinal fluid after intrathecal or radiation chemotherapy

Performance status - ECOG 0-2

At least 4 weeks

Bilirubin no greater than 2 times upper limit of normal* (ULN) (unless due to Gilbert's syndrome)

AST and ALT no greater than 3 times ULN*

Creatinine no greater than 1.5 mg/dL*

No symptomatic congestive heart failure

No unstable angina pectoris

No cardiac arrhythmia

Resting ejection fraction at least 50%*

Not pregnant or nursing

Negative pregnancy test

Fertile patients must use effective contraception

No prior allergy to study medications

No ongoing or active infection requiring IV antibiotics

No other concurrent uncontrolled illness

No serious medical or psychiatric illness that would preclude giving informed consent

More than 4 weeks since prior chemotherapy (except hydroxyurea) (6 weeks for nitrosoureas or mitomycin)

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Please refer to this study by its ClinicalTrials.gov identifier: NCT00070551